Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188549. doi: 10.1016/j.bbcan.2021.188549. Epub 2021 Apr 22.
Molecular targeted therapy of cancer has always been the focus of clinicians. Among those therapeutic targets, the human epidermal growth factor receptor-2 (HER-2) signaling pathway is one of the most popular targets for translational research in cancer. However, unlike prospect in breast cancer, HER-2 inhibitor trastuzumab is the only molecular targeted drug approved by US Food and Drug Administration (FDA) for the first-line treatment of HER-2 positive advanced gastric cancer. On this basis, a variety of novel HER2- targeted drugs for gastric cancer are under development, and related clinical researches are in full swing, including small molecular kinase inhibitors (e.g., afatinib, neratinib, pyrotinib), antibody-drug conjugates (e.g., DS-8201a, RC48-ADC) and other novel therapies (e.g., ZW25, CAR-T, BVAC-B). In this study, we will summarize the recent advances in anti-HER-2 agents, potential mechanisms of resistance to HER2-targeted therapy in HER2-positive gastric cancer. We will also discuss the future prospects of potential strategies to overcome anti-HER-2 resistance and development of novel anti-HER-2 approaches for the treatment of HER2-positive gastric cancer patients.
癌症的分子靶向治疗一直是临床医生关注的焦点。在这些治疗靶点中，人表皮生长因子受体 2（HER-2）信号通路是癌症转化研究中最受欢迎的靶点之一。然而，与乳腺癌不同，HER-2 抑制剂曲妥珠单抗是唯一一种被美国食品和药物管理局（FDA）批准用于 HER-2 阳性晚期胃癌一线治疗的分子靶向药物。在此基础上，针对胃癌的各种新型 HER2 靶向药物正在开发中，相关的临床研究也正在全面展开，包括小分子激酶抑制剂（如阿法替尼、奈拉替尼、吡咯替尼）、抗体药物偶联物（如 DS-8201a、RC48-ADC）和其他新型疗法（如 ZW25、CAR-T、BVAC-B）。在本研究中，我们将总结抗 HER-2 药物的最新进展，以及 HER-2 阳性胃癌中 HER2 靶向治疗耐药的潜在机制。我们还将讨论克服抗 HER-2 耐药的潜在策略的未来前景以及开发新型抗 HER-2 方法治疗 HER-2 阳性胃癌患者的未来前景。
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